EP1608955B1 - Appareil de surveillance en temps reel de reaction biochimique - Google Patents

Appareil de surveillance en temps reel de reaction biochimique Download PDF

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Publication number
EP1608955B1
EP1608955B1 EP04725637.5A EP04725637A EP1608955B1 EP 1608955 B1 EP1608955 B1 EP 1608955B1 EP 04725637 A EP04725637 A EP 04725637A EP 1608955 B1 EP1608955 B1 EP 1608955B1
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EP
European Patent Office
Prior art keywords
light
real
reaction
time monitoring
lamp
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
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EP04725637.5A
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German (de)
English (en)
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EP1608955A4 (fr
EP1608955A1 (fr
Inventor
Jong-Soo Baek
Dong-Yeon Cho
Hanee Park
Han-Oh Park
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Bioneer Corp
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Bioneer Corp
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/06—Means for regulation, monitoring, measurement or control, e.g. flow regulation of illumination
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N21/0332—Cuvette constructions with temperature control
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M31/00—Means for providing, directing, scattering or concentrating light
    • C12M31/02—Means for providing, directing, scattering or concentrating light located outside the reactor
    • C12M31/04—Mirrors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M31/00—Means for providing, directing, scattering or concentrating light
    • C12M31/02—Means for providing, directing, scattering or concentrating light located outside the reactor
    • C12M31/06—Lenses
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6452—Individual samples arranged in a regular 2D-array, e.g. multiwell plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N2021/6484—Optical fibres

Definitions

  • the present invention relates to an apparatus for real-time monitoring chemical reaction between various biomaterials. More particularly, the present invention is directed to a real-time monitoring apparatus for biochemical reaction, which comprises a temperature control block system comprising a thermoelectric element, capable of supplying heat into a reaction tube, a heat transmission block which transmit the heat to the reaction tubes; a light irradiation source part comprising a lamp which irradiates light with uniform intensity to sample contained in the reaction tube, and optical waveguide; and optical system comprising a light receiving part for receiving fluorescence irradiated from the sample by the light emitted from the light irradiation source.
  • a temperature control block system comprising a thermoelectric element, capable of supplying heat into a reaction tube, a heat transmission block which transmit the heat to the reaction tubes
  • a light irradiation source part comprising a lamp which irradiates light with uniform intensity to sample contained in the reaction tube, and optical waveguide
  • optical system comprising a light receiving part for receiving fluor
  • the present invention relates to an apparatus for real-time monitoring chemical reaction between various biomaterials. More particularly, the present invention is directed to a real-time monitoring apparatus for biochemical reaction, which comprises a temperature control block system comprising a thermoelectric element, capable of supplying heat into a reaction tube, a heat transmission block which transmit the heat to the reaction tube; a light irradiation source part comprising a lamp which irradiates light with uniform intensity on sample contained in the reaction tube, and optical waveguide; and optical system comprising a light receiving part for receiving fluorescence irradiated from the sample by the light emitted from the light irradiation source.
  • a temperature control block system comprising a thermoelectric element, capable of supplying heat into a reaction tube, a heat transmission block which transmit the heat to the reaction tube
  • a light irradiation source part comprising a lamp which irradiates light with uniform intensity on sample contained in the reaction tube, and optical waveguide
  • optical system comprising a light receiving part for receiving fluor
  • lab-on-a-chip composed from glass, silicon or plastic material and manufactured through the lithography technology which has been employed for semiconductor chip, mounts micro-sized device for analyzing samples rapidly and sensitively.
  • the above all procedures required for the analysis of sample i.e., pretreatment, reaction, separation, detection and etc., can be performed continuously.
  • the time needed for the sample analysis can be reduced to second or minute level and also the amount of sample can be reduced to microliter level and the size of apparatus on which the chip is mounted can also be miniaturized.
  • the lab-on-a-chip technology is based on the capillary electrophoresis developed by Harrison in early 1990s, and had been started to be known to the public by the fact that a small size lab. Device for the capillary electrophoresis analysis can be integrated into a single chip.
  • the conventional real-time PCR apparatus is composed of the thermoelectric element, the heat transmitting block which transmit heat into reaction tubes which contains sample, the light irradiation source which irradiate light into sample contained in the reaction tube, and the light receiving part which accept the fluorescence generated from the sample.
  • the progress of PCR can be checked in real-time by measuring the intensity of fluorescence generated from sample upon completion of each cycle by the operation of the thermoelectric element for cooling and heating repeatedly to carry out the reaction of biochemical sample contained in the tube.
  • a halogen lamp and a metallic halide lamp have been employed as a light irradiation source.
  • a selective transmission filter (9) transmit selectively the light with preferred wavelength from the light radiated from the lamp (5) and then, the light thus selected irradiated into the sample contained in the tubes via a reflection mirror (18) and through a condensing lens (17).
  • the sample contained in the tubes generate fluorescence by irradiation of light thus selected.
  • the fluorescence thus generated is reflected by reflection mirror (18) and focused through condensing lens (17).
  • the fluorescence thus focused from each tubes is imaged on a light receiving element of the light receiving part to indicate and record the progress of reaction, continuously.
  • the light intensity generated from the light radiation lamp of the conventional apparatus is differentiated depends on the positions, i.e., the center or the edges of the facet of light beam. Consequently, the light intensity generally varied with gaussian curve along with central axis of the facet of light beam and maintain this distribution even through the condensing lens.
  • the primary object of the present invention is to provide an apparatus for real-time monitoring the progress of biochemical reaction, which have technical part to irradiate light with uniform intensity over the whole area of the tube plate which is enlarged than that of prior art.
  • the reaction tube plate of prior art is in general rectangular shape.
  • the conventional light radiation system composed of a lamp and a lens, emits plane wave beam of which facet has round shape.
  • some edge part of light beam should be eliminated to be fitted with the rectangular shaped tube plate. This problem lowers the efficiency of the source due to eliminated pat of light beam.
  • US 4,213,703 discloses a sample holder and shutter assembly for photometers in which a stationary sample chamber body is mounted in close proximity to a photosensitive device. A light path is provided from the sample chamber to the photosensitive device and shutter means is provided for selectively interrupting and opening the light path between the photosensitive device and the sample chamber without moving the sample chamber.
  • Heat exchange means including a heat pump and a heat reservoir are provided for maintaining a desired temperature in the sample chamber.
  • US 6,272,269 discloses a fiber optic illumination system which includes a light source, a waveguide, and an optical fiber.
  • the waveguide includes a straight collecting segment, a tapered condensing segment, and a straight homogenizing segment and conveys light from the light source to the optical fiber by transmission and/or internal reflection.
  • Light transmitted by the optical fiber may be delivered to any one or more of a variety of light output devices, including diffusive flat panels, diffusive rods or wands, fluorescent light emitting converters, projectors, spectrum generators.
  • EP 0 987 540 discloses an imaging device for biochemical or medical samples, the pulse mode light source of which incorporates flash lamps and a rotating mirror in an inclined position, the said mirror reflecting the light emitted by each flash lamp in turn along the same optical path to the sample.
  • the flash lamps are switched on alternately in phases and synchronised with the rotating mirror and the emission light chopper, which comprises two rotating discs.
  • the turning mirror directs the light at the sample from above and/or below.
  • another object of the present invention is to provide a real time monitoring apparatus for biochemical reaction which can irradiate light with uniform intensity over the whole area of the reaction tube plate, even over the whole area of the reaction tube plate enlarged than that of prior art, by irradiating light beam through a light irradiation part via a mirror.
  • the object of the present invention it to provide a real-time monitoring apparatus for biochemical reaction according to the appended claims.
  • Another object of the present invention is to provide a real-time monitoring apparatus for biochemical reaction which has a ellipsoidal mirror associated with the lamp of the apparatus to get an uniform light intensity distribution.
  • the light from the light radiation lamp (5) is focused into the light waveguide (8).
  • the light in the light waveguide is propagated in a manner of total internal reflection.
  • the light beam at the end of the light waveguide (8) become a uniform 2-dimensional light source and are focused on the samples contained in the reaction tubes (4) through the first condensing lens (10).
  • the uniform light beam (31) there reaction progress may be more easily measured over the whole range of the reaction tubes.
  • an apparatus capable of checking the progress of reaction more efficiently may be provided due to the reduced variation of radiation light intensity in each reaction tube by irradiating the light with uniform intensity over broader reaction tube area.
  • the apparatus enables to process uniform reaction information while reacting various samples simultaneously in the reaction tubes.
  • An object of the present invention is to provide a real-time monitoring apparatus for biochemical reaction with improved reaction monitoring sensitivity.
  • the usage efficiency of light source is improved by increasing the amount of light irradiated into the reaction tubes, as the result of minimizing the loss of the light source in prior art by irradiating rectangular light beam adjusted to the aspect ratio of the rectangular reaction tube plate using a light waveguide (8).
  • the present invention relates to a measuring and monitoring apparatus for reaction progress in real-time while reacting various samples.
  • the temperature control block of the present invention is comprised of thermoelectric element (2) for repeating cooling and heating cycles and heat transmission block (3) for transmitting heat to reaction tubes containing samples. Moreover, a radiating plate (1) may be additionally provided for increasing the efficiency of the thermoelectric element.
  • the optical system comprised of a light irradiation source and a light receiving part for measuring the amplified reaction progress in real-time is placed on a temperature control block.
  • the light irradiation source of the present invention comprises a lamp (5) which irradiates light to a sample contained in reaction tubes, a Infra-Red cutting filter (6) intercepting the light from the lamp, an optical waveguide (8) and a first focusing lens (10) for obtaining uniform light beam of the light from the lamp in a wide area, a selective transmission filter 1 (9) for transmitting light of specific wavelength selectively to monitor a reaction progress in the tube, condensing lens 1 (17) for receiving the fluorescence (15) by the radiation light (16) and a second reflective mirror (11) which alters light path.
  • the present invention employs an optical waveguide (8) placed in front of the light source to reduce of the difference in light intensity between the center and the edges of the tube plate and solves the problem of the prior art.
  • the waveguide (8) is designed to irradiate the light beam from the light source uniformly over a wider range.
  • the light beam from the light source experience a total internal reflection due to the refractive indexes between a propagating medium (n2) in the waveguide (8) and surrounding air (nl).
  • the light beam entered into the waveguide (8) forms a uniform plane wave light source at the light outlet (27) thereof.
  • light intensity is more densely distributed in the center and less densely distributed at the edges.
  • the light intensity at the edges is merely about 50- 60% of that in the center. Due to the difference in light intensity, samples placed in the center shows a higher sensitivity and reaction level than the samples placed at the edges by the different amount of light intensity there between.
  • the present invention solves the prior art problem by forming a lamp with parabolic or ellipsoidal mirror as the radiation light source.
  • the optical waveguide (8) is designated to provide light intensity more uniformly over the broader cross-section of light beam.
  • the waveguide (8) employs the difference in refractive indexes between the propagation medium (n2) and surrounding air (nl).
  • Light beam where an incident angle (i) of the incident beam (29) has equal to or larger than a critical angle (c) experience total internal reflection (30) inside the waveguide (8).
  • the incident beam (29) are emitted from the light outlet (27) through the waveguide (8) without loss in light intensity due to the light distribution. In this manner, a highly uniform 2-dimensional light source is formed at the light outlet (27) of the waveguide (8).
  • the refractive index of the propagation medium in the optical waveguide (8) is preferably 1. 35-2. 0.
  • the total internal reflection condition in a medium should satisfy that an incident angle (i) of incident light beam (29) is equal to or bigger than a critical angle (c).
  • reference numeral 30 represents the reflected light beam, 26 for the emitting light beam, and 32 for the refracted light.
  • sin (c) n2 (i (incident angle) > c (critical angle))
  • a plane wave light source of the present invention with uniformly distributed intensity over the cross-section of light beam has more than 85% (21) of light intensity at the edges compared with the light intensity in the center of reaction tube plate (34) and enables to monitor the reaction progress more uniformly by achieving substantially improved light intensity uniformity compared with the prior art.
  • the typical reaction tube plate (34) used for proceeding the reactions of the various biological samples simultaneously is usually a rectangular shape, while the prior art optical radiation system comprising a lamp and a lens generates plane wave light beam with a round-type cross-section.
  • plane wave light beam with a round-type cross-section are adjusted to the shape of the rectangular reaction tube plate (34) and the remaining portions (35) unnecessary for the rectangular shape are removed.
  • the removal of light beam (35) results to the removal of a portions of light beam from the light source lamp and causes graded efficiency of the light source.
  • reference numeral 35 represents the removed light beam.
  • the light waveguide (8) of the present invention has a shape of a rectangular cross-section (37) to be fitted with the aspect ratio of the rectangular plate (34) so that it is able to use the light from the lamp in it maximum efficiency because there are no light beam to be removed.
  • the monitoring sensitivity of present invention is improved by increasing the light intensity irradiated on the plate to more than 20%.
  • the reference numerals 21 and 24 represent the brightness distribution along the X-axis and Y-axis, respectively.
  • Reference numerals 22 and 23 represent the brightness distribution along the X-axis and Y-axis, respectively, of prior art.
  • the radiation light controlled to a plane wave light source shape is irradiated on the samples contained in the reaction tubes (4) placed on the plate through a first focusing lens (10), a first selective transmission filter (9), a second reflecting mirror (11) and a first condensing lens.
  • the nucleic acid samples in the reaction tubes are amplified per every cycle by the temperature block and fluorescence is generated from the amplified samples by the radiation light.
  • the light receiving part of the present invention comprises a second focusing mirror (13) imaging fluorescence (15) from the samples contained in the reaction tubes (4) to the direction of an imaging element by the first condensing lens (17) and the second reflecting mirror (11); a light receiving element (12) for recoding the imaged figure by the second focusing lens (13) and a second selective transmission filter (14) .
  • the fluorescence (15) generated from the samples is imaged on the light receiving element (12) by a second focusing lens (13) through the condensing lens 1 (17), the reflecting mirror 2 (11) and the second selective transmission filter (14).
  • the images by fluorescence of each sample are transferred to a computer which analyzes the changing reaction progress per every cycle. Furthermore, it is possible to compare and analyze while per each sample by reacting various biochemical samples in the reaction tube plate described analyzing the reaction progress for each sample.
  • the real-time monitoring apparatus for biochemical reaction of the present invention employs the lamp (5) with the ellipsoidal-type mirror and the optical waveguide (8), and there may be capable of monitoring the biological reaction progress with uniform sensitivity over the whole reaction plate area over the whole reaction plate (34).
  • the present invention efficiently performs the comparative analysis of various samples while reacting the various samples simultaneously on one reaction tube plate by monitoring the reaction progress of the samples contained in the reaction tubes between the center and the edges of the reaction tube plate, more accurately.
  • the reaction progress of the samples contained in the reaction tubes is equal to in the center and at the edges while there are limitations when performing a comparative analysis of the reaction progress for the samples due to the difference in light intensity of measured fluorescence.
  • the present invention overcomes the limitation of prior art. Therefore, the real-time monitoring apparatus for biochemical reaction of the present invention is able to provide an appropriate apparatus for performing a comparative analysis of the reaction progress of the various samples by minimizing variation of light detection sensitivity during the reaction in the reaction tube plate.
  • the present invention provides a profile of the light beam from the light source which is adjusted to a rectangular shape to be fitted with the aspect ration of the rectangular shape of the reaction tube plate.
  • This adjusted profile of the present invention excludes the necessity of removing some portions of the light beam in the prior art and enables to use the light beam from the light source lamp at the maximum efficiency which improves energy efficiency of the present apparatus accordingly.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Sustainable Development (AREA)
  • Genetics & Genomics (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Thermal Sciences (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Claims (4)

  1. Appareil de surveillance en temps réel de réactions biochimiques, qui consiste en :
    - une plaque rectangulaire de tube de réaction (34) capable de contenir des tubes de réaction ;
    - un bloc de régulation de température comprenant un élément thermoélectrique (2) capable de fournir de la chaleur dans les tubes de réaction et un bloc de transmission de chaleur (3) qui transmet la chaleur aux tubes de réaction ;
    - une source d'irradiation lumineuse, qui irradie une lumière d'une intensité uniforme aux échantillons contenus dans les tubes de réaction, comprenant une lampe (5), et un guide d'onde optique (8), qui a une coupe transversale rectangulaire ajustée au rapport de forme de la plaque rectangulaire de tube de réaction ;
    - un système optique comprenant un premier miroir réfléchissant (7), une première lentille de condensation (10), un second miroir réfléchissant (11), et une seconde lentille de condensation (17), dans lequel le second miroir réfléchissant (11) modifie le trajet lumineux passant à travers au moins une extrémité du guide d'onde optique pour fournir une conception optique repliée, dans lequel l'ordre des éléments optiques dans le trajet optique est la lampe (5), le premier miroir réfléchissant (7), le guide d'onde optique (8), la première lentille de condensation (10), le second miroir réfléchissant (11), et la seconde lentille de condensation (17) ; et
    - une partie réceptrice (12, 13, 14) pour la réception, par le second miroir réfléchissant (11), d'une fluorescence irradiée depuis l'échantillon par la lumière émise depuis la source d'irradiation lumineuse.
  2. Appareil de surveillance en temps réel selon la revendication 1, dans lequel la lampe (5) inclut un miroir réfléchissant parabolique ou ellipsoïdal.
  3. Appareil de surveillance en temps réel selon la revendication 1, dans lequel l'indice de réfraction d'un milieu du guide d'onde optique est de 1,35 à 2,0.
  4. Appareil de surveillance en temps réel selon la revendication 2, comprenant en outre une lentille de focalisation (36) lorsque la lampe (5) est pourvue d'un miroir parabolique.
EP04725637.5A 2003-04-03 2004-04-03 Appareil de surveillance en temps reel de reaction biochimique Expired - Lifetime EP1608955B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
KR20030021145 2003-04-03
KR2003021145 2003-04-03
PCT/KR2004/000785 WO2004088291A1 (fr) 2003-04-03 2004-04-03 Appareil de surveillance en temps reel de reaction biochimique

Publications (3)

Publication Number Publication Date
EP1608955A1 EP1608955A1 (fr) 2005-12-28
EP1608955A4 EP1608955A4 (fr) 2007-09-05
EP1608955B1 true EP1608955B1 (fr) 2020-04-29

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EP04725637.5A Expired - Lifetime EP1608955B1 (fr) 2003-04-03 2004-04-03 Appareil de surveillance en temps reel de reaction biochimique

Country Status (6)

Country Link
US (1) US8139210B2 (fr)
EP (1) EP1608955B1 (fr)
JP (1) JP4751821B2 (fr)
KR (1) KR100794703B1 (fr)
CN (1) CN1798969B (fr)
WO (1) WO2004088291A1 (fr)

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KR101089045B1 (ko) * 2007-06-28 2011-12-02 (주)바이오니아 핵산증폭반응 산물의 실시간 모니터링장치
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KR101840530B1 (ko) 2016-01-08 2018-05-04 고려대학교 산학협력단 표면 측정 센싱 기반의 실시간 핵산 증폭 측정 장치
WO2018191252A1 (fr) * 2017-04-10 2018-10-18 Cornell University Système et procédé d'amplification isotherme d'acides nucléiques
KR102379488B1 (ko) * 2020-07-30 2022-03-25 한림대학교 산학협력단 형광 집광이 가능한 중합효소 연쇄반응 형광 검출 장치 및 이의 형광 집광 장치, 방법 및 프로그램

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EP1608955A4 (fr) 2007-09-05
CN1798969A (zh) 2006-07-05
JP2006522330A (ja) 2006-09-28
EP1608955A1 (fr) 2005-12-28
US20060145098A1 (en) 2006-07-06
WO2004088291A1 (fr) 2004-10-14
KR100794703B1 (ko) 2008-01-14
CN1798969B (zh) 2012-12-26
JP4751821B2 (ja) 2011-08-17
US8139210B2 (en) 2012-03-20
KR20060009246A (ko) 2006-01-31

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